Sex-based differences in saquinavir pharmacology and virologic response in AIDS Clinical Trials Group study 359

AIDS Clinical Trials Group study 359 was a controlled study of saquinavir with either ritonavir or nelfinavir, together with delavirdine, adefovir, or both, in indinavir-experienced persons. Saquinavir was common in all study arms, and the study investigated relationships among characteristics of patients, saquinavir area under the curve (AUC) and trough concentrations (C-min), and virologic response. Concentrations of saquinavir were higher when it was combined with ritonavir than when it was combined with nelfinavir and were lower with adefovir-containing regimens. Females had higher AUC and C-min values than did males. Higher saquinavir AUC and C-min values were associated with a greater likelihood of human immunodeficiency virus (HIV) RNA levels less than or equal to 500 copies/mL (P = .008) and were better predictors of response than was the saquinavir inhibitory quotient. Males had a lower probability of having HIV RNA levels less than or equal to 500 copies/mL at week 16 than did females (28% vs. 42%; adjusted odds ratio, 0.43). In this study, a greater proportion of females had HIV RNA levels less than or equal to 500 copies/mL than did males, which can be attributed to higher concentrations of saquinavir in females than in males.